METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC
Abstract Recently, some methyltransferase-like (METTL) proteins have been found to play crucial roles in the development of acute myeloid leukemia (AML) through mediating RNA modifications, such as METTL3/14/16 mediated N6-methyladenosine (m6A) and METTL1 mediated N7-methylguanosine (m7G). However,...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-05-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02512-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849744685699956736 |
|---|---|
| author | Kui Zhao Hanyue Zhang Shuoting Wang Yuhang Zhou Zhishuai Zhang Baoqiang Kang Huaisong Lin Yanqi Zhang Jiaming Gu Carla Pantoja Lingling Liu Yi He Guangjin Pan Yongli Shan Bing Long |
| author_facet | Kui Zhao Hanyue Zhang Shuoting Wang Yuhang Zhou Zhishuai Zhang Baoqiang Kang Huaisong Lin Yanqi Zhang Jiaming Gu Carla Pantoja Lingling Liu Yi He Guangjin Pan Yongli Shan Bing Long |
| author_sort | Kui Zhao |
| collection | DOAJ |
| description | Abstract Recently, some methyltransferase-like (METTL) proteins have been found to play crucial roles in the development of acute myeloid leukemia (AML) through mediating RNA modifications, such as METTL3/14/16 mediated N6-methyladenosine (m6A) and METTL1 mediated N7-methylguanosine (m7G). However, the roles of other METTL proteins in AML progression remain unknown. Here, we examined the expression levels of all METTL members in AML samples and showed that METTL13 was increased in AML and positively correlated with poor prognosis. Moreover, METTL13 deficiency impaired AML cell proliferation capability in vitro, improved the survival of AML cell line xenograft immune-deficient mice, and reduced tumor infiltration in vivo. Mechanistically, MYC was downregulated after METTL13 knockdown and forced expression of MYC rescued the cell proliferation defect in METTL13-deficient AML cells. Our findings uncover the critical role of METTL13 in the survival of AML cells and identify MYC as a potential downstream target of METTL13. This work highlights METTL13 as a promising candidate target for AML therapy. |
| format | Article |
| id | doaj-art-6d57bc152fa44c788631d3593e5e4367 |
| institution | DOAJ |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-6d57bc152fa44c788631d3593e5e43672025-08-20T03:10:13ZengNature Publishing GroupCell Death Discovery2058-77162025-05-0111111010.1038/s41420-025-02512-xMETTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYCKui Zhao0Hanyue Zhang1Shuoting Wang2Yuhang Zhou3Zhishuai Zhang4Baoqiang Kang5Huaisong Lin6Yanqi Zhang7Jiaming Gu8Carla Pantoja9Lingling Liu10Yi He11Guangjin Pan12Yongli Shan13Bing Long14Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Hematology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Hematology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Gastroenterology, The Eighth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesDepartment of Cell Biology, Yale UniversityDepartment of Hematology, The Third Affiliated Hospital, Sun Yat-sen UniversityDepartment of Hematology, The Third Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesDepartment of Hematology, The Third Affiliated Hospital, Sun Yat-sen UniversityAbstract Recently, some methyltransferase-like (METTL) proteins have been found to play crucial roles in the development of acute myeloid leukemia (AML) through mediating RNA modifications, such as METTL3/14/16 mediated N6-methyladenosine (m6A) and METTL1 mediated N7-methylguanosine (m7G). However, the roles of other METTL proteins in AML progression remain unknown. Here, we examined the expression levels of all METTL members in AML samples and showed that METTL13 was increased in AML and positively correlated with poor prognosis. Moreover, METTL13 deficiency impaired AML cell proliferation capability in vitro, improved the survival of AML cell line xenograft immune-deficient mice, and reduced tumor infiltration in vivo. Mechanistically, MYC was downregulated after METTL13 knockdown and forced expression of MYC rescued the cell proliferation defect in METTL13-deficient AML cells. Our findings uncover the critical role of METTL13 in the survival of AML cells and identify MYC as a potential downstream target of METTL13. This work highlights METTL13 as a promising candidate target for AML therapy.https://doi.org/10.1038/s41420-025-02512-x |
| spellingShingle | Kui Zhao Hanyue Zhang Shuoting Wang Yuhang Zhou Zhishuai Zhang Baoqiang Kang Huaisong Lin Yanqi Zhang Jiaming Gu Carla Pantoja Lingling Liu Yi He Guangjin Pan Yongli Shan Bing Long METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC Cell Death Discovery |
| title | METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC |
| title_full | METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC |
| title_fullStr | METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC |
| title_full_unstemmed | METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC |
| title_short | METTL13 is essential for the survival of acute myeloid leukemia cells by regulating MYC |
| title_sort | mettl13 is essential for the survival of acute myeloid leukemia cells by regulating myc |
| url | https://doi.org/10.1038/s41420-025-02512-x |
| work_keys_str_mv | AT kuizhao mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT hanyuezhang mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT shuotingwang mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT yuhangzhou mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT zhishuaizhang mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT baoqiangkang mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT huaisonglin mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT yanqizhang mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT jiaminggu mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT carlapantoja mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT linglingliu mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT yihe mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT guangjinpan mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT yonglishan mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc AT binglong mettl13isessentialforthesurvivalofacutemyeloidleukemiacellsbyregulatingmyc |